Non-Infectious Transfusion Reactions
(minus TRALI)
Transfusion Medicine
Eiad Kahwash,MD,FASCP
Transfusion Reactions
• ANY unfavorable consequence is
considered a transfusion reaction of
blood TX
• The risks of transfusion must be
weighed against the benefits
Transfusion Reactions
1.
Acute (<24 hours) Transfusion Reactions - Immunologic
–
2.
Acute Transfusion Reactions - Nonimmunologic
–
3.
Hemolytic (Physical or Chemical destruction of RBC); Circulatory
overload; Air embolus; Hypocalcemia; Hypothermia
Delayed (>24 Hours) Transfusion Reaction - Immunologic
–
4.
Hemolytic ; Graft vs. Host Disease; Posttransfusion Purpura
Delayed Transfusion Reactions - Nonimmunologic
–
5.
Hemolytic; Febrile-non hemolytic; Allergic; Anaphylactic;
Transfusion Reaction of Acute Lung injury(TRALI)
Iron Overload
Infectious Complications of Blood Transfusion
Acute (<24 hours) Transfusion Reactions
1. Immunologic
– Hemolytic; Febrile-non hemolytic;
Allergic; Anaphylactic; Transfusion
Reaction of Acute Lung injury(TRALI)
2. Nonimmunologic
– Volume overload; Hemolytic (Physical
or Chemical destruction of RBC); Air
embolus; Hypocalcaemia; Hypothermia
Acute Transfusion Reactions
Immunologic
Acute Hemolytic Transfusion Reaction
• Associated with Intravascular
Hemolysis
• Etiology: Antibodies that activate
complements in the vasculature: ABO
antibodies are predominant / not the
only ones.
• Prevention: Give ABO compatible blood.
Acute Transfusion Reactions
Immunologic
• May also occur due to ABO incompatible
plasma in platelet products
• Very rare; less than 20 case reports, all
involving group O platelets
• Usually occurs in group A patients or those
with anti-A titers greater than 1:1000
• Can prevent by removing plasma from
platelets, or limiting number of incompatible
group O platelets in a 24 hour period
(Archives 2007;131:909)
Intravascular Hemolysis
Characteristics
• Within minutes
• IgM &/or IgG
antibody
• Complement
activation
• Release of histamine
and serotonin
Signs may include:
•
•
•
Pain along infusion site
Shock
Abnormal
bleeding/DIC/
Hemoglobinemia/uria
•
Release of cytokines:
•
Renal failure/ Oliguria,
fever, hypotension
may progress to…anuria
Acute Transfusion Reactions
Immunologic
Febrile non-hemolytic TX
Reactions
• An INCREASE in temperature of 1OC during
infusion of blood component
– Usually “mild & benign” = not life threatening
– Can have more severe symptoms, not usually
• Non-hemolytic
• Incidence of 0.1% of RBC transfusions, 0.1-1.0% of
platelet transfusions
• Cause: Recipient antibodies to donor WBCs &
Cytokines in the transfused blood component.
Febrile Transfusion Reactions
Seen in…
• Multiply transfused patients
• Multiple pregnancies
• Previously transplanted
Must rule out…
• Hemolytic transfusion reaction
• Bacterial contamination of unit
Prevention
• Leukocyte reduction
(pre-storage reduction may be
more effective than post-storage reduction) or plasma
removal is also helpful.
Acute Transfusion Reactions
Immunologic
Allergic (Urticarial-Hives)
Transfusion Reactions
• Etiology: Form of cutaneous
hypersensitivity triggered by recipient
antibodies directed against:
– Donor plasma proteins or
– Other allergens (food, medicines) in donor
plasma
• Begins within minutes of infusion
• Characterized by rash and/or hives and
itching .
• Common (1 per 2000 transfusions)
• Usually involves release of histamine.
Allergic (Urticarial) Reactions
• MUST be sure that the only reaction is the
development of urticaria
• Must rule out more severe symptoms that
could lead to anaphylaxis:
– angioneurotic edema
– laryngeal edema
– bronchial asthma
• Prevention: Can pre-treat recipient with
anti-histamines before transfusion.
(Transfus Med Rev 2007;21:1, Br J Haematol 2005;130:781) .
Acute Transfusion Reactions
Immunologic
Anaphylaxis
• Life threatening!!
• Etiology:
– Recipient is IgA deficient & has anti-IgA in serum
– Recipient anti-IgA can react to even small amounts of
donor IgA in the plasma in any blood component
– Idiopathic &Haptoglobin deficiency
• Reaction may occur within minutes : Onset of symptoms is
SUDDEN
• Prevention:
Wash cellular components or blood
products from IgA deficients
Acta Anaesthesiol Scand 2002;46:1276
Anaphylaxis
Symptoms
• Burning sensation at infusion site
• Coughing, difficulty in breathing, and
bronchospasms can lead to cyanosis
• Nausea, vomiting, severe abdominal cramps,
diarrhea
• Hypotension which can lead to shock, loss of
consciousness, & death
• MUST STOP TX IMMEDIATELY
Acute Transfusion Reactions
Immunologic
TX Reaction of Acute Lung Iinjury
Etiology:
• Acute onset of hypoxemia and pulmonary
edema on CX-RAY within 6 hrs of TX without
evidence of cardiac failure.
Mechanism’s
• Primary Suspect: Donor antibodies to
recipient WBCs
• Another cause: Biologically active lipids in the
lungs causing edema
Transfusion Reaction of Acute
Lung Injury(TRALI)
• Symptoms
• Chills, fever, cough, cyanosis,
hypotension, increased difficulty
breathing
• Prevention: For recipients : give male
products- For donors: watch/defer.
Acute Transfusion Reactions
NONimmunologic
Circulatory Overload
• Etiology: Rapid increases in blood volume to
patient .Risk factors: compromised cardiovascular function, current
volume overload, small intravascular volume (elderly, young children), severe
chronic anemia.
Signs and Symptoms
• Dyspnea, cyanosis, severe headaches,
hypertension or CHF (congestive heart
failure). Chest Xray: pulmonary edema, distended pulmonary artery,
cardiomegaly
• Laboratory: elevated B-natriuretic peptide (BNP) is 81%
sensitive and 89% specific (Transfusion 2005;45:1056)
• Prevention: Slow Tx. Treatment: Stop
infusion and place patient in sitting
position.
Archives 2007;131:708
Acute Transfusion Reactions
NONimmunologic
Physically or Chemically Induced
Red Cell Destruction
Etiology:
• Destruction of red blood cells in the collection
bag and infusion of free hemoglobin, etc.
Improper temperatures: High or Low
• Microwave blood bag, malfunctioning blood warmer
or water bath, inadvertent freezing of blood.
Physically or Chemically Induced
Red Cell Destruction
Osmotic Hemolysis
• Addition of drugs or hypotonic solutions
(5% dextrose, deionized water, etc.) to
transfusion.
•
•
•
•
Mechanical Hemolysis
Caused by rollers in blood pump
Pressure infusion pumps
Small bore needles
Prevention: Adherence to procedures for
all aspects of procuring, processing, issuing
and administering red blood cell
transfusions.
Acute Transfusion Reactions
NONimmunologic
Hypocalcemia
• Excess citrate: When infused at rate >100
mL/minute or individuals with impaired liver
function:
– Citrate is broken down by liver.
• Seen more in pediatric and elderly patients
• Signs and Symptoms: Facial tingling, nausea,
vomiting.
• Prevention: Slowing or discontinuing infusion.
Acute Transfusion Reactions
NONimmunologic
Hypothermia
• Etiology: Drop in core body temperature due
to rapid infusion of large volumes of cold
blood.
• Symptoms: Decreased body temperature and
ventricular arrhythmias.
• Seen in small infants or massive transfusion
• Prevention: Reduce rate of infusion or use
blood warmers.
Acute Transfusion Reactions
NONimmunologic
Air Embolism
• Etiology: If blood in an open system is
infused under pressure or if air enters
the system while container or blood
administration sets are being changed.
• Treatment: Place patient on left side
with head down to displace air bubble
from pulmonic valve.
1. Acute (<24 hours) Transfusion Reactions - Immunologic
–
Hemolytic; Febrile-non hemolytic; Allergic; Anaphylactic;
Transfusion Reaction of Acute Lung injury(TRALI)
2. Acute Transfusion Reactions - Nonimmunologic
–
Volume overload; Hemolytic (Physical or Chemical destruction of
RBC); Air embolus; Hypocalcemia; Hypothermia
3. Delayed (>24 Hours) Transfusion Reaction - Immunologic
–
Hemolytic ; Graft vs. Host Disease; Posttransfusion Purpura
4. Delayed Transfusion Reactions - Nonimmunologic
–
Iron Overload
5. Infectious Complications of Blood Transfusion
Delayed (>24 Hours) Transfusion Reaction 1. Immunologic
– Hemolytic ; Graft vs. Host Disease;
Posttransfusion Purpura
2. Nonimmunologic
– Iron Overload
Delayed Transfusion Reactions
Immunologic
Delayed Hemolytic Transfusion
Reaction (Red blood cell alloimmunization)
• Onset within days (>24 hours)
• Associated with Extravascular
Hemolysis
• Etiology: Antibodies that usually do NOT
activate Complements : Rh, Kell, etc.
• Prevention: Give antigen negative blood.
Extravascular Hemolysis
•
•
•
•
Characteristics
Signs may include:
Reaction within days
• No release of free
Hgb, or enzymes into
Antibody attaches to
circulation
RBC: RBC destroyed
in spleen or liver, etc. • May be immediate
(hours) or delayed
Commonly IgG
(days)
May or may not
activate Complement • Bilirubinemia or
bilirubinuria
Extravascular Hemolysis
Signs & Symptoms continued…
1. Fever or fever & chills
2. Jaundice
3. Unexpected anemia
•
Some may present as an ABSENCE of
an anticipated increase in Hemoglobin
and hematocrit.
Delayed Transfusion Reaction
Immunolgic
Graft vs Host Disease (GVHD)
• Etiology: Donor CD8+ T-Lymphocytes attack
recipient (host) tissues. Very rare in blood stored 4+ days due
to WBC inactivation (Br J Haematol 2000;111:146)
• Groups at risk:
– Immunocompromised patients (Cancer,
fetus, neonatal, bone marrow transplant).
• Signs: Fever, dermatitis, or erythroderma,
hepatitis, diarrhea, pancytopenia, etc.
• Prevention: Irradiation of blood products.
Osaka City Med J 1999;45:37
Delayed Transfusion Reaction
Immunolgic
Post-transfusion Purpura
• Etiology: Antibodies to platelet antigens (HP1a )
causes abrupt onset of severe thrombocytopenia
(platelet count <10,000/l) 5-10 days following
transfusion. Usually affects multiparous women .
• Signs: Purpura, bleeding, fall in platelet count
.
treatment: IVIG, plasmapheresis or
corticosteroids; platelet transfusions usually
NOT recommended
Transfus Med 2006;16:69
Delayed Transfusion Reaction
NONimmunolgic
Iron Overload
•
•
•
Etiology: Excess iron resulting from
chronically transfused patients such as
hemoglobinopathies, chronic renal failure, etc.
Signs: Muscle weakness, fatigue, weight loss,
mild jaundice, anemia, etc.
Treatment: Infusion of deferoxamine - an iron
chelating agent has been useful.
1. Acute (<24 hours) Transfusion Reactions - Immunologic
–
Hemolytic; Febrile-non hemolytic; Allergic; Anaphylactic;
Transfusion Reaction of Acute Lung injury(TRALI)
2. Acute Transfusion Reactions - Nonimmunologic
–
Volume overload; Hemolytic (Physical or Chemical destruction of
RBC); Air embolus; Hypocalcemia; Hypothermia
3. Delayed (>24 Hours) Transfusion Reaction - Immunologic
–
Hemolytic ; Graft vs. Host Disease; Posttransfusion Purpura
4. Delayed Transfusion Reactions - Nonimmunologic
–
Iron Overload
5. Infectious Complications of Blood Transfusion
Infectious Complications
of
Blood Transfusion
(Viral is rare)
Infectious Complication of
Blood Transfusion
Bacterial Contamination
• Etiology: At time of collection: either
from the donor or the venipuncture
site.
– During component preparation, etc.
• Usually involves endotoxins
– Staph, Pseudomonas, E.coli, Yersinia
Bacterial Contamination
• Components: Most often from platelet
components (room temp). Red cell units
will look dark.
• Symptoms: Rapid onset
– Fever, hypotension, shaking chills,
muscle pain
– Vomiting, abdominal cramps, bloody
diarrhea, hemoglobinuria, shock, renal
failure, & DIC.
Bacterial Contamination
Transfusion must be stopped immediately
• Gram stain & blood cultures should be done
on the unit, patient and all infusion sets .
• Broad-spectrum antibiotics should be given
immediately intravenously
• Prevention: Maintain standards of donor
selection, blood collection and proper
maintenance of collected blood components.
Transfusion Reactions
1. Acute (<24 hours) Transfusion Reactions - Immunologic
–
Hemolytic; Febrile-non hemolytic; Allergic; Anaphylactic;
Transfusion Reaction of Acute Lung injury(TRALI)
2. Acute Transfusion Reactions - Nonimmunologic
–
Volume overload; Hemolytic (Physical or Chemical destruction of
RBC); Air embolus; Hypocalcemia; Hypothermia
3. Delayed (>24 Hours) Transfusion Reaction - Immunologic
–
Hemolytic ; Graft vs. Host Disease; Posttransfusion Purpura
4. Delayed Transfusion Reactions - Nonimmunologic
–
Iron Overload
5. Infectious Complications of Blood Transfusion
Transfusion Reaction
Follow-up
Clinical Information Needed:
•
•
•
•
•
Recipient diagnosis
Medical history of pregnancy &/or transfusion
Current medications
Signs & symptoms during transfusion reaction
How many mL’s of RBC’s or plasma were
transfused?
Clinical Information Needed
•
•
•
•
Were rbc’s cold or warm when transfused?
Were red cells infused under pressure?
What was the size of the needle used?
Were other solutions given through the IV
line at the same time? If so what?
• Were any other drugs given at the time of
transfusion? If so, what?
• What were pre- & post- transfusion vital
signs?
Transfusion Reaction Follow-up
Post Transfusion Reaction blood samples
to be collected from the recipient:
• Clotted specimen
• EDTA specimen
• Clotted specimen
• 1st voided urine
specimen post-tx’n
• Repeat ABO, Rh, IAT and
Crossmatch. Visual check for
hemolysis and compare with pre
transfusion sample.
• DAT (Direct Antiglobulin Test)
• Collect 5-7 hours post
transfusion to check for
bilirubin
• Free hemoglobin determination
Transfusion Reaction Workup
CLERICAL CHECKS
1. Correct
identification of
patient, specimen,
and transfused unit.
2. Agreement of
records and history
with current results
3. Correct labeling of
transfused unit
SPECIMEN
CHECKS
• Visual inspection of
post-transfusion
specimen
• Visual inspection of
blood bag and lines
Post Transfusion Lab Testing
Direct Antiglobulin Test (DAT)
• Recipient post-tx’n spec.
• Positive: Perform eluate and identify antibody
if the pre-TX spec negative.
ABO Grouping and Rh Typing
• Recipient pretransfusion and posttransfusion
specimen
• Donor bag.
Post Transfusion Lab Testing
Indirect Antiglobulin Test
(IAT)
• Recipient Pre- & post-transfusion
reaction specimens
• Pre neg and post pos: Identify
antibody and compare results of
serum panel with eluate panel.
In Summery:
1-Allergic: Minor VS Serious
2-Febrile: Minor VS Serious
3-Onset<15 Mints,Temp>1C with other
symptoms orTemp>39C, BP , Shock,SOA,
Rigors, Back/Chest Pain,Bleeding from IV
site, Tachy/Arrhythmia, Nausea/Vomiting
and Generalized Flushing
In Summery:
1-
Stop TX immediately and keep an IV
open with 0.9 Saline
2-Contact the clinician
3-Check vital signs every 15 minutes
4-Check labels,forms,and Ids
5-Send bags &patient’s blood to BB
6-Minor(allergic-febrile non-hemolytic)
VS Serious (hemolytic &febrile)
Questions?
Thank You